Mouse Intestinal Krt15+ Crypt Cells Are Radio-Resistant and Tumor Initiating

作者：Giroux Veronique; Stephan Julien; Chatterji Priya; Rhoades Ben; Wileyto E Paul; Klein Szanto Andres J; Lengner Christopher J; Hamilton Kathryn E; Rustgi Anil K^*

来源：Stem Cell Reports, 2018, 10(6): 1947-1958.

DOI：10.1016/j.stemcr.2018.04.022

Two principal stem cell pools orchestrate the rapid cell turnover in the intestinal epithelium. Rapidly cycling Lgr5+ stem cells are intercalated between the Paneth cells at the crypt base (CBCs) and injury-resistant reserve stem cells reside above the crypt base. The intermediate filament Keratin 15 (Krt15) marks either stem cells or long-lived progenitor cells that contribute to tissue repair in the hair follicle or the esophageal epithelium. Herein, we demonstrate that Krt15 labels long-lived and multipotent cells in the small intestinal crypt by lineage tracing. Krt15+ crypt cells display self-renewal potential in vivo and in 3D organoid cultures. Krt15+ crypt cells are resistant to highdose radiation and contribute to epithelial regeneration following injury. Notably, loss of the tumor suppressor Apc in Krt15+ cells leads to adenoma and adenocarcinoma formation. These results indicate that Krt15 marks long-lived, multipotent, and injury-resistant crypt cells that may function as a cell of origin in intestinal cancer.

• 出版日期2018-6-5